Alimentary immune function Flashcards

1
Q

What is the surface area of the GI tract?

A

400m^2

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2
Q

What is the dual immunological role of the GI?

A

Must maintain tolerance to food antigens and commensal bacteria and an active immune response for pathogens. It is therefore in a constant state of ‘restrained activation’.

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3
Q

What immunological purpose does the microbiota have?

A

require it for development of healthy immune system

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4
Q

How many microbes in gut?

A

10^14

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5
Q

state 4 major phyla of microbiota

A

Bacteriodetes, firmicutes, Actinobacteria, proteobacteria.

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6
Q

Where are microbiota most abundant?

A

Colon, where there are no host digestive factors (e.g. enzymes, gastric acid…).

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7
Q

3 types of microbiota? Dynamics between the three?

A

SYMBIONTS: take up energy, but provide help and regulation; COMMENSALS: function not known but prevent pathogens binding to epithelium and outcompete; PATHOBIONTS capable of causing inflammation. ………………………….. These are in balance - called immunological equilibrium.

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8
Q

What is the name when microbiota classes are disturbed?

A

Dysbiosis, altered numbers of pathobionts caused by an immunological event e.g. pathogen invasion –> leads to inflammation.

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9
Q

What are causes of dysbiosis? (x5)

A

Infection, diet, xenobiotics, hygiene and genetics, as well as infection or even diet.

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10
Q

What is issue with dysbiosis?

A

Can result in large amounts of bacterial metabolites and toxins produced: this can have far reaching effects, and result in systemic diseases of the adipose, liver, lung and even brain.

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11
Q

What are physical barriers against infection. (x2 (x3))

A

PHYSICAL ANATOMICAL BARRIERS: Epithelial barrier with tight junctions, mucous layer, paneth cells of small intestine (bases of crypts of Lieberkuhn secrete antimicrobial peptides and lysozyme.

PHYSICAL CHEMICAL BARRIER: pH in stomach, enzymes.

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12
Q

What is the second “line of defence/barrier” against infection

A

Commensal bacteria

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13
Q

What form of defence does the tract have incase of breach by bacteria?

A

MALT (Mucosa associated lymphoid tissue) and GALT (Gut) which are immunoogical.

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14
Q

Where and what are MALT found?

A

In the submucosa (below the epithelium) as lymphoid mass containing lymphoid follicles.

Follicles are surrounded by HEV post-capillary venules, allowing for easy passage of lymphocytes.

Some found in mouth eg pharengeal tonsils

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15
Q

Where is GALT found and what types are there (x2)? IMMUNOLIGCAL FUNCTION?

A

Responsible for adaptive AND innate immune responses.

Found in organised and non-organised forms.

Non-organised: Intra-epithelial lymphocytes – Make up one-fifth of intestinal epithelium, e.g., T cells, NK cells Lamina propria lymphocytes

Organised: Peyer’s patches (small intestine) Caecal patches (large intestine) Isolated lymphoid follicles Mesenteric lymph nodes (encapsulated).

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16
Q

What is the structure of Peyer’s Patches?

A

Found in small intestine – mainly distal ileum.

  • Aggregated lymphoid follicles covered with follicle associated epithelium (FAE).
  • Organised collection of naïve T cells and B-cells.
  • Associated with M (microfold) cells which are found within FAE.
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17
Q

What is the function of Peyer’s patches? How do M cells perform their function?

A

Development requires exposure to bacterial microbiota (50 in last trimester foetus, 250 by teens).

  • Antigen uptake via M (microfold) cells within FAE.
  • M cells therefore sample antigens. M cells then present these antigens to the patches and activate them.
  • M cell transfers bacteria for phagocytosis in patches.

HOW DO M-CELLS TRANSFER? M cells express IgA receptors, facilitating transfer of IgA-bacteria complex into the peyer’s patches.

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18
Q

What is FAE?

A

Epithelium covering mucosa-associated lymphoid tissue (MALT).

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19
Q

What is lamina propria?

A

Thinlayer of connective tissue that forms part of the moist linings known as mucous membranes or mucosa, which line various tubes in the body, such as the respiratory tract, the gastrointestinal tract, and the urogenital tract.

This is where lymphocytes migrate in circumstances of infection. Antibodies are then secreted into the lumen of the GIT from the lamina propria.

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20
Q

Describe characteristics of Follicle associated epithelium (FAE). (x3)

A

no goblet cells, no secretory IgA, lack microvilli.

21
Q

What does M cell stand for?

A

Microfold cells

22
Q

What are trans-epithelial dendritic cells?

A

An example of trans-epithelial antigen sampling in the gut. Have long extensions which penetrate through the epithelium and samples antigens. They bring antigens back and transfer them to mysenteric lymph nodes.

23
Q

Describe in stages, the B Cell adaptive response

A
  1. Mature naïve B-cells express IgM in Peyer’s Patches.
  2. Upon antigen presentation class switch to IgA.
  3. T-cells & epithelial cells influence B cell maturation via cytokine production.
  4. B cells further mature to become IgA secreting plasma cells.
  5. Populate lamina propria.
24
Q

Describe pathway of secretory IgA formation.

A

Plasma cells produce dimer IgA which bind to to Poly-Ig receptor on basolateral membrane.

The dimer-receptor complex is endocytosed and cleaved to liberate the receptor so that it can be returned to the membrane.

Then, Iga has secretory component attached which provides protection for the antibody against harsh environment of the gut .

A secretory dimer is then released into the gut.

25
Q

WHAT IS THE PURPOSE OF sIgA?

A

Bind to luminal antigens and prevent adhesion to epithelial lining and thereby protecting against invasion. This is known as protection through NEUTRALISATION.

26
Q

Describe difference between small and large intestine epithelial layer. (x2)

A

SI: larger crypts, less mucus. LI: smaller crypts, produces two layers of mucus, so that bacteria cannot enter.

27
Q

What is the most common GALT found in the LI?

A

Caecal Patch

28
Q

Describe lymphocyte circulation.

A

TRAVEL FROM THE PEYER’S PATCH FROM WHICH THEY ORIGINATE and travel to mesenteric lymph node –> thoracic duct and into the circulation….

Then there are two routes for the lymphocytes:

  1. IF ACTIVATED: go back to the organ for which it originated to fight pathogen (in lamina propria).
  2. IF NAIVE: goes to other lymphoid organs (tonsils, BALT, Skin…) via HEV.
29
Q

What is lymphocyte homing?

A

The directed migration of subsets of circulating lymphocytes into particular tissue sites.

Process relies on linkage between adhesion molecules expressed on endothelial cells and their ligands expressed on lymphocytes. Homing receptor on T lymohocytes are involved in this.

30
Q

Describe 3 stages of lymphocyte entering lamina propia.

A
  1. Rolling (weak selectin binding);
  2. Activation (strong intergrin);
  3. Arrest (and enters).
31
Q

Which surface molecules lead to activation and arrest

A

Integrin on lymphocyte, and MAdCAM-1 on epithelial cell

32
Q

Describe mechanism of cholera infection

A

Caused by Vibrio Cholerae, releases cholera toxin at small intestine, causes release of Na, Cl, K into lumen; water follows and leads to diarrhoea.

33
Q

What are the symptoms of cholera?

A

Severe dehydration and watery diarrhoea.

Also associated with nausea, vomiting and abdominal pain.

34
Q

How is cholera transmitted?

A

Faeco-oral route, dirty water/food

35
Q

How is cholera diagnosed? (x2)

A

Bacterial culture from stool sample, and rapid dipstick tests also available.

36
Q

How is cholera treated?

A

Oral rehydration and Dukoral is an oral, inactivated vaccine.

37
Q

Other causes of diarrhoea? (x3 (x2, x2 and x5))

A

Viral: Rotavirus and Norovirus

Protozoal: Giardia lamblia, Entaoeba histolytica

Bacterial: Campylobacter Jejuni, E-coli, Salmonella, Shigella, Chlostridium Dificile.

38
Q

Description of Rotavirus: What? Types? Epidemiology? Treatment?

A

Description: RNA virus, replicates in enterocytes.

5 types A – E, type A most common in human infections.

Epidemiology: Most common cause of diarrhoea in infants and young children worldwide.

Treatment: oral rehydration therapy, but still cause about 200,000 deaths per year. Before vaccine, most individuals had an infection by age 5, repeated infections develop immunity.
Vaccination: Live attenuated oral vaccine (Rotarix) against type A introduced in UK July 2013.

39
Q

Description of Norovirus: What? Diagnosis? Epidemiology? Transmission?

A

Description: RNA virus. Incubation period 24-48 hours.

Diagnosis: Sample PCR.

Epidemiology: Estimated 685 million cases per year.

Transmission: Faecal-oral transmission. Individuals may shed infectious virus for up to 2 weeks. Outbreaks often occur in closed communities.

40
Q

Description of Campylobacter: Types? Transmission? Epidemiology? Treatment?

A

Most common species: Campylobacter jejuni, Campylobacter coli

Transmission: Undercooked meat (especially poultry), untreated water and unpasteurised milk. Low infective dose, a few bacteria (<500) can cause illness.

Epidemiology: Estimated 280,000 cases per year in UK, 65,000 confirmed. Most common cause of food poisoning in the UK.

Treatment: Not usually required, azithromycin (macrolide) is standard antibiotic, resistance to fluoroquinolones is problematic

41
Q

E coli description (6 types)

A

Diverse group of Gram negative intestinal bacteria, most harmless but 6 ”pathotypes” have been identified that are associated with diarrhoea (diarrhoeagenic):

  • Enterotoxigenic E. coli (ETEC): Cholera like toxin, Watery diarrhea
  • Enteroinvasive E. coli (EIEC): Shigella like illnes, Bloody diarrhea
  • Enterohaemorrhagic or Shiga toxin-producing E. coli (EHEC/STEC): E. coli O157 serogroup, Shigatoxin/verotoxin, 5-10% get haemolytic uraemic syndrome: loss of kidney function
  • Enteropathogenic E. coli (EPEC)
  • Enteroaggregative E. coli (EAEC)
  • Diffusely adherent E. coli (DAEC)
42
Q

How do you treat Clostridium Dificile? (x3)

A
  • Isolate patient (very contagious)
  • Stop current antibiotics Metronidazole, Vancomycin
  • Faecal Microbiota Transplantation (FMT) – 98% cure rate
43
Q

What is Coeliac disease and how does it work? Symptoms? Diagnosis? Management?

A

Autoimmune disorder.

Gliadin is a 33aa peptide component of gluten that is not broken down in the stomach, reaches small intestine, binds to sIgA and is transferred to the lamina propria.

B cells are activated, there is cytokine production and autoantibodies produced and intestinal inflammation as a result.

SYMPTOMS: Abdominal distension (bloating) Diarrhoea

DIAGNOSIS: Ab blood tests - anti-gliadin. Biopsy test of duodenum

MANAGEMENT: Diet management – gluten-free diet (wheat, barley, rye exclusion).

44
Q

What is irritable bowel syndrome: Mechanism? Symptoms? Treatment?

A

MECHANISM: unknown, but we do know that it is cause by (1) vsceral hypersensitivity and (2) triggered by diet / stress.

SYMPTOMS: Recurrent abdominal pain Abnormal bowel motility Constipation and/or Diarrhoea

TREATMENT: Diet modification - Avoiding certain foods such as apples, beans, cauliflowers. Treatment of constipation - soluble fiber, stool softeners and osmotic laxatives. Treatment of spasms and pain - anti-diarrheals, anti-muscarinic. Management of stress, anxiety, depression.

45
Q

What two diseases come under INFLAMMATORY (not irritable) BOWEL DISEASE?

A

Crohn’s and ulcerative colitis.

46
Q

What are the genetic (x3) and environmental (x5) factors that cause INFLAMMATORY bowel disease?

A

Genetic factors: production of chemokines, cytokines, antimicrobial peptides.

Environmental factors: dysbiosis, diet, smoking, antibiotics, stress…

47
Q

What is the pathophysiology of INFLAMMATORY bowel disease?

A

Destruction of epithelial lining and entry of pathogens into lamina propria.

These pathogens consequently activate immune response and regulation fails = chronic inflammation which leads to fibrosis and even colon cancer.

48
Q

Description of Crohn’s: Location? Pathology? Symptoms? Diagnosis? Treatment?

A

Location: ileum and colon

Pathology: Patches of inflammatory damage and healthy tissue, “cobblestone” appearance

Symptoms: Diarrhoea, abdominal cramping, fever, anaemia, weight loss & fatigue

Diagnosis: Antibody blood tests, endoscopy, Barium x-ray (contrast)

Treatment: Anti-inflammatory drugs Immunosuppressants Surgery (not curative)

49
Q

Ulcerative colitis description: Location? Pathology? Symptoms? Diagnosis? Treatment?

A

Location: Colon

Pathology: Continuous inflammation

Symptoms: Bloody diarrhoea, abdominal cramping, anaemia, weight loss and fatigue

Diagnosis: Antibody blood tests, endoscopy, Barium x-ray (contrast)

Treatment: Anti-inflammatory drugs Immunosuppressants Colectomy (curative)